Process for making



United States Patent 13 Claims. :1. 260-240) The present inventionrelates to a process for the preparation of ,B[2-(5-substituted) furyl]propionic acid esters by cleavage of B-f'urfurylidene ketones in theabsence of water and the compounds produced thereby.

A cleavage of the furan ring in B-furfurylidene ketones has beendescribed by Kehrer and Igler in Ber. 32, 1176 (1899), but Kehrer andIgler conducted their cleavage in the presence of water, concentratedhydrochloric acid and alcohol and thereby obtained an addition oraccumulation of 2 moles of water while the w-substituted heptanedione-(4,7)-dioic acid esters and, respectively, their acids were formed.

It has now been found that fi[2-(5-substituted) furyl] propionic acidesters of the general formula wherein R is a C H CH or C H -CH:CH groupand R designates an aliphatic primary alcohol residue, may be preparedin a simple manner by splitting ,B-furfurylidene ketones of the generalformula wherein R has the above-indicated significance, with excessamounts, preferably the triple to quadruple amount, of water-free,monohydric, saturated aliphatic alcohols with up to 8 carbon atoms inthe presence of dry, purified acids, preferably gaseous HCl, in amountsof 0.5 up to 5%, preferably in amounts of 12% and at temperatures ofbetween 70 and 120 0, preferably of from 100ll0 C., in an inertatmosphere, such as nitrogen, with the addition of hydroquinone or otherantioxidants in amounts of O.11%, and more particularly in amounts of").61%, expediently while stirring and separating by distillation theresulting carboxylic acid esters which are rendered impure bynon-reacted starting material of the general formula The reaction mayalso be carried out in a sealed tube at temperatures of from 200-250 C.The higher temperature may be utilized due to the exclusion of air andthus the prevention of oxidation reactions. The reaction time may beshortened in relation to the temperature increase. The advantages of thesealed tube are, however, limited, since such tubes are relativelysmall.

As fi-furfurylidene ketones, fi-furyl-acrylophenone, furfural acetoneand benzylidene furfurylidene acetone, for example, may be used.

As monohydric saturated aliphatic alcohols, methanol, propanol, butanol,heptanol, etc., may be used.

The present invention, accordingly, has as its principle 3 2,210,344Patented Oct. 5, 1965 object, the production of B[2-(5-substituted)furyl] propionic acid esters.

Other objects will become apparent as the description proceeds.

The ,B-furfurylidene ketones of the above-mentioned type are, accordingto the present invention, dissolved in excess amounts of absolute,monohydric, saturated aliphatic alcohols, which have been previouslyreacted, for example, with 11.5% gaseous, dried hydrochloric acid, andheated in a nitrogen atmosphere in the presence of hydroquinone for 5-7hours while stirring. If necessary, another inert solvent, such asbenzene, chloroform, and methylene chloride, may also be used. Theduration of heating and the temperature depend upon the species orvariety of the alcohol used. In order to avoid an air oxidation, it maybe advantageous, particularly for the reaction of smaller amounts towork in the sealed tube as mentioned above.

The esters produce according to the present invention are obtained, inaddition to non-reacted starting material, by the subsequentdistillation. When the resulting esters, according to the presentinvention, contain a phenyl residue in the 5-position, and when aneffective fractionation is impossible due to the close boiling points,purification and removal of the non-reacted starting material may beachieved by hydration thereof with any type of nascent hydrogen (Na/alcohol, and, respectively, Zn/ Hg) or with Raney nickel in an autoclaveat 15-30 atmospheres, preferably 2025 atmospheres, and at temperaturesof from 70120 0, preferably from -l10 C. During such an operation, thestarting product present as impurity will be hydrated to lower boilingconstituents which may be then easily separated from the esters bydistillation.

It is possible to produce other compounds from the carboxylic estersprepared according to the present invention, in a manner known in theart, for example, ,8[2-(5-substituted) furyl] propionic acid. Inaddition, they may be utilized as starting materials for the preparationof any other derivatives of the acids on which the esters of the presentinvention are based. The products prepared or produced according to thepresent invention also serve as intermediate products in polymerizationand polycondensation reactions.

The following examples serve to illustrate the present invention,without limiting the same.

Example I 230 g. B-furyl-acrylophenone are stirred in. 750 g. 1.5% HClcontaining absolute n-butanol while introducing N in the presence of0.8% of hydroquinone for 7 hours at C. After distillation of the excessbutanol, the main amount of the non-reacted ,B-furylacrylophen-one isdistilled in vacuo at 2 mm. to 168 C. (100 g). At 170-175 C. (2 mm.), g.of the yellow-colored butyl ester additionally pass over.

Example II 300 g. p[2-5(phenyl) furyl] propionic acid butyl ester arehydrated with 300 cc. methanol and 1 g. Raney nickel in an autoclave at22 atmospheres hydrogen and 100 C. to the end of the hydrogenabsorption. After distillation of the methanol, the residue isfractionated in an oil pump vacuum over a small Vigreux column. Thereby,810 g. of a colorless preliminary run (boiling point 80150 C.) areobtained, while 270 g. of the pure, greenish-yellow butyl ester comeover at a boiling point of 178-180 C. Saponification with alcoholic KOHyields the corresponding carboxylic acid. The melting point of theproduct is 116 to 117 C. and consists of needles having a water-whitewith a lightly greenish coloration.

3 Example III 400 g. of fi-furyl-acrolophenone are stirred in 2 litersof absolute iso-octanol containing 2% water-free ptoluene-sulfonic acidwhile introducing N in the presence of 0.8% hydroquinone for 10 hours at100-110" C. After distillation of the excess octanol in a water jetvacuum, the main amount of the non-reacted ,B-furyl-acrylophenone isdistilled ofi in vacuo at 2 mm. up to 168 C. (210 g.). Between 138-140C. (0.2 mm.), an additional 180 g. of the deeply yellow-colorediso-octanol ester pass over.

Example IV 330 g. furfural acetone are stirred in 800 cc. absolutebutanol, containing 1% H01, while introducing CO in the presence of 1%pyrogallol for 6 hours at 8595 C. After distillation of the excessbutanol, most favorably in a water jet vacuum, 80 g. of the non-reactedfurfural acetone are distilled off between 75-77 C. (1.5 mm.), while atbetween 132135 C. (1.5 mm.), 30 g. of the yellow butyl ester pass over.The residue is a solid, insoluble, black mass.

Example V 60 g. benzylidene furfurylidene acetone are dissolved in 240ml. of absolute butanol and 50 ml., dried CHCl and added drop-wiseduring 3 hours at 100 C. while stirring at 330 ml. of absolute butanolcontaining 1.8% HCl, dried at a high temperature. After another 3-4hours, the butanol and the hydrochloric acid are removed at 15 Torr, andthe black, oily residue distilled at as low as possible a pressure.Thereby, only the deeply yellow-colored butyl ester passes over in ayield which is 23% of the theoretical (18 g.) between 191-1 92 C. and0.8 Torr, while the starting ketone changes very rapidly into a brittle,resinous mass.

While I have described my invention with reference to the abovediscussion and examples, it will be understood that I do not wish to belimited thereto since many modifications may be made by one skilled inthe art within the scope of the invention, and I intend to include allsuch modifications which come within the scope of the appended claims.

I claim:

1. A process for the preparation of B-[Z-(S-substituted furyl] propionicacid esters of the general formula wherein R is a radical selected fromthe group consisting of C H CH and C H CH:CH and R is an aliphaticprimary alcohol residue, comprising cleaving a ,B-furfurylidene ketoneof the general formula wherein R has the above-indicated meaning, withan excess amount of a water-free, monohydric, saturated, aliphaticalcohol of up to 8 carbon atoms in the presence of between approximately0.5 and 5% of a dry, purified acid at an elTective elevated temperature,and thereafter separating the resulting carboxylic acid ester productfrom the reaction mixture.

2. A process in accordance with claim 1, wherein the cleavage isconducted in an inert atmosphere and in the presence of betweenapproximately 0.1 to 1.0% of an antioxidant.

3. A process in accordance with claim 2, wherein the insert atmosphereis nitrogen and the antioxidant is hydroquinone.

4. A process in accordance with claim 1, wherein the resultingcarboxylic acid ester product is separated from the reaction mixture bydistillation.

5. A process in accordance with claim 1, wherein the ,B-furfurylideneketone is selected from the group consisting of p-furyl-acrylophenone,furfural acetone, and benzylidene furfurylidene acetone.

6. A process in accordance with claim 1, wherein the cleavage isconducted at a temperature of from approximately to 120 C.

'7. A process in accordance with claim 1, wherein R is a phenyl groupand wherein, prior to the separation step, the unreacted startingmaterial in the resulting reaction mixture is hydrated by treating thesame with a compound selected from the group consisting of nascenthydrogen and Raney nickel in an autoclave at a pressure of betweenapproximately 15 and 30 atmospheres and a temperature of approximately70 to 120 C.

8. A process for the preparation of fl-[Z-(S substituted) furyl]propionic acid esters of the general formula wherein R is a radicalselected from the group consisting of C H CH,;,, and C H CH:CH- and R isan aliphatic primary alcohol residue, comprising dissolving a[B-furfurylidene ketone of the general formula wherein R has theabove-indicated meaning, with an excess amount of a water-free,monohydric, saturated, aliphatic alcohol of up to 8 carbon atoms in thepresence of between 0.5 and 5% of a dry, purified acid, heating thesolution thereof to an elfective elevated temperature, and thereafterseparating the resulting carboxylic and ester product from the reactionmixture.

9. A process in accordance with claim 8, wherein an inert solventselected from the group consisting of benzene, chloroform, and methylenechloride is also used to dissolve the fi-furfurylidene ketone.

10. A process for the preparation of ,8-[2-(5-substituted furyl]propionic acid esters of the general formula wherein R is a radicalselected from the group consisting of c,H CH and C H CH:CH and R is analiphatic primary alcohol residue, comprising cleaving aB-furfurylid'ene ketone of the general formula CH-CH wherein R has theabove-indicated meaning, with an excess amount of a water-free,monohydric, saturated, aliphatic alcohol of up to 8 carbon atoms in thepresence of between 1 and 2% of dry, purified HCl at a temperature ofbetween approximately and C. in the presence of an inert atmosphere andbetween approximately 0.1 and 1% of an antioxidant, and thereafterseparating the resulting carboxylic acid ester product from the reactionmixture.

11. A process for the preparation of {3-[2-(5substituted) furyl]propionic acid esters of the general formula wherein R is a radicalselected from the group consisting of C H CH and C H -CH:CH- and R is analiphatic primary alcohol residue, comprising cleaving afl-furfurylidene ketone of the general formula CH-(II| H RCo011=cH- CHwherein R has the above-indicated meaning, with an excess amount of aWater-free, monohydric, saturated, aliphatic alcohol of up to 8 carbonatoms in the presence of between approximately 0.5 and 5% of a dry,purified acid at a temperature of between approximately 200 and 250 C.in a sealed tube in an inert atmosphere and in the presence of betweenapproximately 0.1 and 1% of an antioxidant, and thereafter separatingthe resulting carboxylic acid ester product from the reaction mixture.

12. fi-[Z-(S-phenyl) furyl] propionic acid isooctyl ester. 13.fl-[Z-(S-styryl) furyl] propionic acid butyl ester.

References Cited by the Examiner FOREIGN PATENTS 1,278,631 11/61 France.

6 OTHER REFERENCES Blicke et al. J. Am. Chem. Soc., vol. 66, page 1677Chemical Abstracts, vol. 49, col. 6904 (1955) (abstract 5 of Yamashitaet al., J. Chem. Soc. Japan, Indust. Chem.

Section, vol. 56, pages 811-14 (1953)).

Chemical Abstracts Decennial Index (1947 to 1956) page 5403 s of subjectindex under Z-furanpropionic acid (1960).

Dunlop et al., The Furans, pages 48, 52, 590 to 591, 653 to 658, 674 to679 and 686 to 690, Reinhold Publishing Corp. (1953).

Robinson et al. J. Chem. Soc., 1939, pages 1743 to 1747.

Turner, J. Am. Chem. Soc., vol. 71, pages 612 to 615 (1949).

WALTER A. MODANCE, Primary Examiner.

20 JOHN D. RANDOLPH, Examiner.

1. A PROCESS FOR THE PREPARATION OF B-(2(5-SUBSTITUTED FURYL)) PROPIONICACID ESTERS OF THE GENERAL FORMULA
 13. B-(2-(5-STYRYL) FURYL) PROPIONICACID BUTYL ESTER.